Medical Specialties Commons^™

Genome-Wide Crispr Screen Reveals The Synthetic Lethality Between Bcl2l1 Inhibition And Radiotherapy, Ling Yin, Xiaoding Hu, Guangsheng Pei, Mengfan Tang, You Zhou, Huimin Zhang, Min Huang, Siting Li, Jie Zhang, Citu Citu, Zhongming Zhao, Bisrat G Debeb, Xu Feng, Junjie Chen

Faculty, Staff and Student Publications

Radiation therapy (RT) is one of the most commonly used anticancer therapies. However, the landscape of cellular response to irradiation, especially to a single high-dose irradiation, remains largely unknown. In this study, we performed a whole-genome CRISPR loss-of-function screen and revealed temporal inherent and acquired responses to RT. Specifically, we found that loss of the IL1R1 pathway led to cellular resistance to RT. This is in part because of the involvement of radiation-induced IL1R1-dependent transcriptional regulation, which relies on the NF-κB pathway. Moreover, the mitochondrial anti-apoptotic pathway, particularly the BCL2L1 gene, is crucially important for cell survival after radiation. BCL2L1 …

Risk Of Developing Hypertension In Atopic Dermatitis Patients Receiving Long-Term And Low-Dose Cyclosporine: A Nationwide Population-Based Cohort Study, Yu Ri Woo, Arum Choi, Seo Won Song, Suyeun Kim, Sang Wook Son, Sang Hyun Cho, Sukil Kim, Jung Eun Kim

Faculty, Staff and Student Publications

BACKGROUND: Cyclosporine (CS) is a first-line immunosuppressive agent used to manage moderate to severe atopic dermatitis (AD). To date, the risk of developing hypertension associated with the long-term use of low-dose CS in AD patients is understudied.

OBJECTIVE: To determine the cumulative dose-dependent effect of CS on the risk of developing hypertension in patients with AD.

METHODS: A nationwide population-based retrospective cohort with 1,844,009 AD patients was built from the Korean National Health Insurance System database from 2005 to 2009. A Cox proportional-hazard regression analysis was performed according to patients' CS treatment history adjusted for potential confounders.

RESULTS: Current use …

Primary Health Care And The Tanzania Comprehensive Cancer Project, Gijs Walraven, Harrison Chuwa, Alain Fourquet, Paschal Ruggajo

Internal Medicine, East Africa

No abstract provided.

Automatic End-To-End Vmat Treatment Planning For Rectal Cancers, Kai Huang, Christine Chung, Ethan B Ludmir, Lifei Zhang, Constance A Owens, Jean Gumma-De La Vega, Jack Duryea, Yao Zhao, Xinru Chen, David Fuentes, Carlos E Cardenas, Tina Marie Briere, Sam Beddar, Laurence E Court, Prajnan Das

Faculty, Staff and Student Publications

BACKGROUND: The treatment planning process from segmentation to producing a deliverable plan is time-consuming and labor-intensive. Existing solutions automate the segmentation and planning processes individually. The feasibility of combining auto-segmentation and auto-planning for volumetric modulated arc therapy (VMAT) for rectal cancers in an end-to-end process is not clear.

PURPOSE: To create and clinically evaluate a complete end-to-end process for auto-segmentation and auto-planning of VMAT for rectal cancer requiring only the gross tumor volume contour and a CT scan as inputs.

METHODS: Patient scans and data were retrospectively selected from our institutional records for patients treated for malignant neoplasm of the …

Risk Factors For In-Hospital Seizure And New-Onset Epilepsy In Coiling And Clipping Treatment Of Aneurysmal Subarachnoid Hemorrhage, Viet-Thang Le, Anh Minh Nguyen, Phuc Long Nguyen

Faculty, Staff and Student Publications

OBJECTIVE: To identify risk factors associated with in-hospital seizures and new-onset epilepsy in patients with aneurysmal subarachnoid hemorrhage (SAH) who underwent coiling embolization or clipping surgery.

METHODS: This retrospective descriptive study included 195 patients diagnosed with aneurysmal SAH and treated with coiling embolization or clipping surgery between January 2018 and June 2022.

RESULTS: Among the 195 patients meeting inclusion criteria, 9 experienced an onset seizure at the time of SAH. In-hospital seizures were observed in 33 patients, of which 24 were electrographic seizures detected in 24 patients with suspected subclinical seizures. After 12 months of follow-up, 11 patients met criteria …

Abatacept Pharmacokinetics And Exposure Response In Patients Hospitalized With Covid-19, Stephen J Balevic, Daniel K Benjamin, William G Powderly, P Brian Smith, Daniel Gonzalez, Matthew W Mccarthy, Linda K Shaw, Christopher J Lindsell, Sam Bozzette, Daphne Williams, Benjamin P Linas, John Blamoun, Heta Javeri, Christoph P Hornik

Faculty, Staff and Student Publications

IMPORTANCE: The pharmacokinetics of abatacept and the association between abatacept exposure and outcomes in patients with severe COVID-19 are unknown.

OBJECTIVE: To characterize abatacept pharmacokinetics, relate drug exposure with clinical outcomes, and evaluate the need for dosage adjustments.

DESIGN, SETTING, AND PARTICIPANTS: This study is a secondary analysis of data from the ACTIV-1 (Accelerating COVID-19 Therapeutic Interventions and Vaccines) Immune Modulator (IM) randomized clinical trial conducted between October 16, 2020, and December 31, 2021. The trial included hospitalized adults who received abatacept in addition to standard of care for treatment of COVID-19 pneumonia. Data analysis was performed between September 2022 …

Lymphocyte-Activation Gene 3 Facilitates Pathological Tau Neuron-To-Neuron Transmission, Chan Chen, Ramhari Kumbhar, Hu Wang, Xiuli Yang, Kundlik Gadhave, Cyrus Rastegar, Yasuyoshi Kimura, Adam Behensky, Sumasri Kotha, Grace Kuo, Sruthi Katakam, Deok Jeong, Liang Wang, Anthony Wang, Rong Chen, Shu Zhang, Lingtao Jin, Creg J Workman, Dario A A Vignali, Olga Pletinkova, Hongpeng Jia, Weiyi Peng, David W Nauen, Philip C Wong, Javier Redding-Ochoa, Juan C Troncoso, Mingyao Ying, Valina L Dawson, Ted M Dawson, Xiaobo Mao

Faculty, Staff and Student Publications

The spread of prion-like protein aggregates is a common driver of pathogenesis in various neurodegenerative diseases, including Alzheimer's disease (AD) and related Tauopathies. Tau pathologies exhibit a clear progressive spreading pattern that correlates with disease severity. Clinical observation combined with complementary experimental studies has shown that Tau preformed fibrils (PFF) are prion-like seeds that propagate pathology by entering cells and templating misfolding and aggregation of endogenous Tau. While several cell surface receptors of Tau are known, they are not specific to the fibrillar form of Tau. Moreover, the underlying cellular mechanisms of Tau PFF spreading remain poorly understood. Here, it …

Targetable Genetic Abnormalities In Patients With Acute Myeloblastic Leukemia Across Age Groups, Alex Bataller, Courtney D Dinardo, Alexandre Bazinet, Naval G Daver, Abhishek Maiti, Gautam Borthakur, Nicholas Short, Koji Sasaki, Elias J Jabbour, Ghayas C Issa, Naveen Pemmaraju, Musa Yilmaz, Guillermo Montalban-Bravo, Sanam Loghavi, Guillermo Garcia-Manero, Farhad Ravandi, Hagop M Kantarjian, Tapan M Kadia

Faculty, Staff and Student Publications

Incidence of potential targetable genetic abnormalities by age in AML.

Performance Characteristics Of The 5-Ring Ge Discovery Mi Pet/Ct Scanner Using Aapm Tg-126 Report, Refaat Y Almazrou, Shadei F Alanazi, Mohammed H Alzaid, Razan S Al-Fakhranee, Shanli Ding, Osama R Mawlawi

Faculty, Staff and Student Publications

AIM: To report on the performance characteristics of the 5-ring GE Discovery MI PET/CT systems using the AAPM TG-126 report and compare these results to NEMA NU 2-2012 where applicable.

MATERIALS AND METHODS: TG-126 testing was performed on two GE 5-Rings Discovery MI scanners. Tests performed included spatial resolution, PET/CT image-registration accuracy, sensitivity, count rate performance, accuracy of corrections, image contrast, scatter/attenuation correction, and image uniformity. All acquired data were analyzed using scanner console or free software tools as described by TG-126 and the results were then compared to published NEMA NU 2-2012 values.

RESULTS: Both scanners gave similar resolution …

It's About Time! Timing In Epilepsy Evaluation And Treatment, Heather Ravvin Mckee, Jorge Vidaurre, Dave Clarke, Janelle Wagner, Jeffrey W Britton, Linda Laux, Eugen Trinka, Clio Rubinos, Tanya J W Mcdonald, Fred A Lado, Martina Bebin, Christos Papadelis, Aaron F Struck, Carolina B Maciel, Ana L Velasco, Arjun Chandran, Sandipan Pati, Nitin Tandon, Guadalupe Fernandez-Baca Vaca, Madison M Berl, Ahsan N Moosa

Faculty, Staff and Student Publications

The 2023 American Epilepsy Society Annual Course "It's About Time" addressed timing in epilepsy evaluation and treatment with respect to health disparity and vulnerable populations and diagnostic, clinical, and epilepsy surgery evaluation. This comprehensive course included topics on gaps in epilepsy care and optimization of behavioral health for patients with epilepsy. The summary details current knowledge in areas of seizure forecasting and epileptogenesis. Intricacies and controversies over timing were discussed for treatment of nonconvulsive seizures and ictal-interictal patterns, acute symptomatic seizures, neuromodulation versus surgery, and epilepsy surgery in status epilepticus. Timing regarding clinical care in autoimmune-associated epilepsy, developmental and epileptic …

Effect Of Perioperative Stroke On Survival After Carotid Intervention, Tommaso Cambiaghi, Alexander Mills, Samuel Leonard, Regina Husman, Syed T Zaidi, Ezra Y Koh, Kourosh Keyhani, S Keisin Wang

Faculty, Staff and Student Publications

OBJECTIVES: Perioperative stroke is the most dreaded complication of carotid artery interventions and can severely affect patients' quality of life. This study evaluated the impact of this event on mortality for patients undergoing interventional treatment of carotid artery stenosis with three different modalities.

METHODS: Patients undergoing carotid revascularization at participating Memorial Hermann Health System facilities were captured from 2003-2022. These patients were treated with either carotid endarterectomy (CEA), transfemoral carotid stenting (TF-CAS), or transcarotid artery revascularization (TCAR). Perioperative outcomes, including stroke and mortality, as well as follow-up survival data at 6-month intervals, were analyzed and stratified per treatment modality.

RESULTS: …

Transcatheter Electrosurgical Septotomy Technique For Chronic Postdissection Aortic Aneurysms, Aidin Baghbani-Oskouei, Safa Savadi, Thomas Mesnard, Titia Sulzer, Aleem K Mirza, Shadman Baig, Carlos H Timaran, Gustavo S Oderich

Faculty, Staff and Student Publications

Aortic dissection often results in chronic aneurysmal degeneration due to progressive false lumen expansion. Thoracic endovascular aortic repair and other techniques of vessel incorporation such as fenestrated-branched or parallel grafts have been increasingly used to treat chronic postdissection aneurysms. True lumen compression or a vessel origin from the false lumen can present considerable technical challenges. In these cases, the limited true lumen space can result in inadequate stent graft expansion or restrict the ability to reposition the device or manipulate catheters. Reentrance techniques can be used selectively to assist with target vessel catheterization. Transcatheter electrosurgical septotomy is a novel technique …

Case Of Human Orthohantavirus Infection, Michigan, Usa, 2021, Samuel M Goodfellow, Robert A Nofchissey, Dustin Arsnoe, Chunyan Ye, Seonghyeon Lee, Jieun Park, Won-Keun Kim, Kartik Chandran, Shannon L M Whitmer, John D Klena, Jonathan W Dyal, Trevor Shoemaker, Diana Riner, Mary Grace Stobierski, Kimberly Signs, Steven B Bradfute

Faculty, Staff and Student Publications

Orthohantaviruses cause hantavirus cardiopulmonary syndrome; most cases occur in the southwest region of the United States. We discuss a clinical case of orthohantavirus infection in a 65-year-old woman in Michigan and the phylogeographic link of partial viral fragments from the patient and rodents captured near the presumed site of infection.

Oncolytic Adenoviruses And Immunopeptidomics: A Convenient Marriage, Marc Garcia-Moure, Andrew G Gillard, Marta M Alonso, Juan Fueyo, Candelaria Gomez-Manzano

Faculty, Staff and Student Publications

Oncolytic viruses (OVs) are biological therapeutic agents that selectively destroy cancer cells while sparing normal healthy cells. Besides direct oncolysis, OV infection induces a proinflammatory shift in the tumor microenvironment and the release of tumor-associated antigens (TAAs) that might induce an anti-tumor immunity. Due to their immunostimulatory effect, OVs have been explored for cancer vaccination against specific TAAs. However, this approach usually requires genetic modification of the virus and the production of a new viral vector for each target, which is difficult to implement for low prevalent antigens. In a recent study, Chiaro et al. presented an elegant proof of …

Effectiveness Of A Training Program For The Management Of Risky Alcohol Use In Primary Care Professionals Based On Motivational Interviewing, Celia Pérula-Jiménez, Esperanza Romero-Rodríguez, Juan Manuel Parras-Rejano, Ana González De La Rubia, Juan Baleato Gómez, Luis Angel Pérula De Torres

Faculty, Staff and Student Publications

OBJECTIVE: To assess the effectiveness of a training program for Primary Care (PC) professionals developed to increase knowledge, attitudes, and skills for managing patients with risky alcohol use and in the motivational interview.

DESIGN: Multicenter, two-arm parallel, randomized, open-label controlled clinical trial.

SETTING: PC of the Andalusian Health Service.

PARTICIPANTS: The study was completed by 80 healthcare professionals from 31 PC centers.

INTERVENTIONS: In both experimental and control groups, a workshop on managing patients with risky alcohol consumption and the resolution of two videotaped clinical cases with standardized patients were conducted. The experimental group attended a workshop on motivational interviewing. …

Intraprocedural Versus Initial Follow-Up Minimal Ablative Margin Assessment After Colorectal Liver Metastasis Thermal Ablation: Which One Better Predicts Local Outcomes?, Yuan-Mao Lin, Iwan Paolucci, Jessica Albuquerque Marques Silva, Caleb S O'Connor, Bryan M Fellman, Aaron K Jones, Joshua D Kuban, Steven Y Huang, Zeyad A Metwalli, Kristy K Brock, Bruno C Odisio

Faculty, Staff and Student Publications

Objectives: The aim of this study was to investigate the prognostic value of 3-dimensional minimal ablative margin (MAM) quantified by intraprocedural versus initial follow-up computed tomography (CT) in predicting local tumor progression (LTP) after colorectal liver metastasis (CLM) thermal ablation.

Materials and methods: This single-institution, patient-clustered, tumor-based retrospective study included patients undergoing microwave and radiofrequency ablation between 2016 and 2021. Patients without intraprocedural and initial follow-up contrast-enhanced CT, residual tumors, or with follow-up less than 1 year without LTP were excluded. Minimal ablative margin was quantified by a biomechanical deformable image registration method with segmentations of CLMs on intraprocedural preablation …

Dose-Dense Mini-Hyper-Cvd, Inotuzumab Ozogamicin And Blinatumomab Achieves Rapid Mrd-Negativity In Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia, Nicholas J Short, Elias Jabbour, Trevor Jamison, Shilpa Paul, Branko Cuglievan, David Mccall, Amber Gibson, Nitin Jain, Fadi G Haddad, Lewis F Nasr, Kayleigh R Marx, Caitlin Rausch, J Michael Savoy, Rebecca Garris, Farhad Ravandi, Hagop Kantarjian

Faculty, Staff and Student Publications

Background: The combination of low-intensity chemotherapy and inotuzumab ozogamicin (INO), with sequential blinatumomab, is highly effective in older adults with newly diagnosed B-cell acute lymphoblastic leukemia (ALL) and in relapsed or refractory B-cell ALL. Earlier, "dose-dense" administration of blinatumomab could lead to earlier and deeper measurable residual disease (MRD) responses and better outcomes.

Patients and methods: We performed a retrospective analysis of the safety and efficacy of a dose-dense regimen of mini-hyper-CVD (mini-hyperfractionated cyclophosphamide, vincristine, and dexamethasone alternating with mini-methotrexate and cytarabine), INO, and blinatumomab in patients with B-cell ALL.

Results: Twenty-one patients were treated (frontline, n = 9; MRD …

Chromatin Remodeling In Patient-Derived Colorectal Cancer Models, Kun Xiang, Ergang Wang, John Mantyh, Gabrielle Rupprecht, Marcos Negrete, Golshid Sanati, Carolyn Hsu, Peggy Randon, Anders Dohlman, Kai Kretzschmar, Shree Bose, Nicholas Giroux, Shengli Ding, Lihua Wang, Jorge Prado Balcazar, Qiang Huang, Pasupathi Sundaramoorthy, Rui Xi, Shannon Jones Mccall, Zhaohui Wang, Chongming Jiang, Yubin Kang, Scott Kopetz, Gregory E Crawford, Steven M Lipkin, Xiao-Fan Wang, Hans Clevers, David Hsu, Xiling Shen

Faculty, Staff and Student Publications

Patient-Derived Organoids (PDO) and Xenografts (PDX) are the current gold standards for patient-derived models of cancer (PDMC). Nevertheless, how patient tumor cells evolve in these models and the impact on drug response remains unclear. Herein, the transcriptomic and chromatin accessibility landscapes of matched colorectal cancer (CRC) PDO, PDX, PDO-derived PDX (PDOX), and original patient tumors (PT) are compared. Two major remodeling axes are discovered. The first axis delineates PDMC from PT, and the second axis distinguishes PDX and PDO. PDOX are more similar to PDX than PDO, indicating the growth environment is a driving force for chromatin adaptation. Transcription factors …

Disease Progression, Survival, And Molecular Disparities In Black And White Patients With Endometrioid Endometrial Carcinoma In Real-World Registries And Gog/Nrg Oncology Randomized Phase Iii Clinical Trials, Zachary A Kopelman, Chunqiao Tian, Jordyn Tumas, Neil T Phippen, Christopher M Tarney, Erica R Hope, Stuart S Winkler, Suzanne Jokajtys, Calen W Kucera, John K Chan, Michael T Richardson, Daniel S Kapp, Chad A Hamilton, Charles A Leath, Nathaniel L Jones, Rodney P Rocconi, John H Farley, Angeles Alvarez Secord, Casey M Cosgrove, Matthew A Powell, Ann Klopp, Joan L Walker, Gini F Fleming, Nicholas W Bateman, Thomas P Conrads, G Larry Maxwell, Kathleen M Darcy

Faculty, Staff and Student Publications

OBJECTIVE: Investigate racial disparities in outcomes and molecular features in Black and White patients with endometrioid endometrial carcinoma (EEC).

METHODS: Black and White patients diagnosed with EEC who underwent hysterectomy ± adjuvant treatment in SEER, National Cancer Database (NCDB), the Genomics Evidence Neoplasia Information Exchange (GENIE) project (v.13.0), and eight NCI-sponsored randomized phase III clinical trials (RCTs) were studied. Hazard ratio (HR) and 95% confidence interval (CI) were estimated for cancer-related death (CRD), non-cancer death (NCD), and all-cause death.

RESULTS: Black (n = 4397) vs. White (n = 47,959) patients in SEER had a HR (95% CI) of 2.04 (1.87-2.23) …

Clinical Epidemiological Characteristics And Risk Factors For Severity Of Sars-Cov-2 Pneumonia In Pediatric Patients: A Hospital-Based Study In Vietnam, Sang N Nguyen, Lam T Vu, Ha T Nguyen, Giang H Dao, Anh Ngoc T Nguyen

Faculty, Staff and Student Publications

Introduction Coronavirus disease (COVID-19) is an infectious disease caused by SARS-CoV-2, which can cause organ failure in several organs, cardiac problems, or acute respiratory distress syndrome (ARDS). Identifying clinical epidemiological characteristics and risk factors for complications of COVID-19 allows clinicians to diagnose and treat promptly. Objectives This study aims to describe the clinical epidemiological characteristics of COVID-19 and assess risk factors for the severity of SARS-CoV-2 pneumonia in children treated at Haiphong Children's Hospital. Methods A descriptive cross-sectional study was conducted in Haiphong Children's Hospital, Haiphong, Vietnam, for one year, from January 1, 2022, to December 31, 2022. Results In …

Normal Risk Ovarian Screening Study: 21-Year Update, Chae Young Han, Karen H Lu, Gwen Corrigan, Alexandra Perez, Sharlene D Kohring, Joseph Celestino, Deepak Bedi, Enrique Bedia, Therese Bevers, David Boruta, Matthew Carlson, Laura Holman, Leroy Leeds, Cara Mathews, Georgia Mccann, Richard G Moore, Matthew Schlumbrecht, Brian Slomovitz, Dan Tobias, Yvette Williams-Brown, Michael W Bevers, Jinsong Liu, Terrie G Gornet, Beverly C Handy, Zhen Lu, Jacob S Bedia, Steven J Skates, Robert C Bast

Faculty, Staff and Student Publications

Purpose: The Normal Risk Ovarian Screening Study (NROSS) tested a two-stage screening strategy in postmenopausal women at conventional hereditary risk where significantly rising cancer antigen (CA)-125 prompted transvaginal sonography (TVS) and abnormal TVS prompted surgery to detect ovarian cancer.

Methods: A total of 7,856 healthy postmenopausal women were screened annually for a total of 50,596 woman-years in a single-arm study (ClinicalTrials.gov identifier: NCT00539162). Serum CA125 was analyzed with the Risk of Ovarian Cancer Algorithm (ROCA) each year. If risk was unchanged and < 1:2,000, women returned in a year. If risk increased above 1:500, TVS was undertaken immediately, and if risk was intermediate, CA125 was repeated in 3 months with a further increase in risk above 1:500 prompting referral for TVS. An average of 2% of participants were referred to TVS annually.

Results: Thirty-four patients were referred for operations detecting 15 ovarian cancers and two borderline tumors with 12 …

Histologic And Genomic Analysis Of Conjunctival Scc In African And American Cohorts Reveal Uv Light And Hpv Signatures And High Tumor Mutation Burden, Frederico O Gleber-Netto, Priyadharsini Nagarajan, Oded Sagiv, Curtis R Pickering, Neil Gross, Jing Ning, Melisachew M Yeshi, Yonas Mitku, Michael T Tetzlaff, Bita Esmaeli

Faculty, Staff and Student Publications

Purpose: Conjunctival squamous cell carcinoma (conjSCC) is more prevalent and aggressive in sub-Saharan African countries compared with the rest of the world. This study aims to compare the genomic, immunophenotypic, and histologic features between patients from the United States and Ethiopia, to identify etiopathogenic mechanisms and unveil potential treatment strategies.

Methods: We compared histologic features and mutational profiles using whole exome sequencing, high-risk human papillomavirus (HPV) status, PD-L1 expression, and tumor-infiltrating lymphocytes in conjSCC tumors of patients from Ethiopia (ETH; n = 25) and the United States (from MD Anderson [the MDA cohort]; n = 29). Genomic alterations were compared …

Machine Learning-Enabled Maternal Risk Assessment For Women With Pre-Eclampsia (The Piers-Ml Model): A Modelling Study, Tünde Montgomery-Csobán, Kimberley Kavanagh, Paul Murray, Chris Robertson, Sarah J E Barry, U Vivian Ukah, Beth A Payne, Kypros H Nicolaides, Argyro Syngelaki, Olivia Ionescu, Ranjit Akolekar, Jennifer A Hutcheon, Laura A Magee, Peter Von Dadelszen, Piers Consortium

Faculty, Staff and Student Publications

BACKGROUND: Affecting 2-4% of pregnancies, pre-eclampsia is a leading cause of maternal death and morbidity worldwide. Using routinely available data, we aimed to develop and validate a novel machine learning-based and clinical setting-responsive time-of-disease model to rule out and rule in adverse maternal outcomes in women presenting with pre-eclampsia.

METHODS: We used health system, demographic, and clinical data from the day of first assessment with pre-eclampsia to predict a Delphi-derived composite outcome of maternal mortality or severe morbidity within 2 days. Machine learning methods, multiple imputation, and ten-fold cross-validation were used to fit models on a development dataset (75% of …

Seamark: Phase Ii Study Of First-Line Encorafenib And Cetuximab Plus Pembrolizumab For Msi-H/Dmmr Brafv600e-Mutant Mcrc, Elena Elez, Scott Kopetz, Josep Tabernero, Tanios Bekaii-Saab, Julien Taieb, Takayuki Yoshino, Gulam Manji, Kathrine Fernandez, Antonello Abbattista, Xiaosong Zhang, Van K Morris

Faculty, Staff and Student Publications

Patients with both BRAF V600E mutations and microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC) have poor prognosis. Currently, there are no specifically targeted first-line treatment options indicated for patients with mCRC whose tumors harbor both molecular aberrations. Pembrolizumab is a checkpoint inhibitor approved for the treatment of MSI-H/dMMR mCRC, and the BRAF inhibitor encorafenib, in combination with cetuximab, is approved for previously treated BRAF V600E-mutant mCRC. Combination of pembrolizumab with encorafenib and cetuximab may synergistically enhance antitumor activity in patients with BRAF V600E-mutant, MSI-H/dMMR mCRC. SEAMARK is a randomized phase II study comparing the efficacy of the combination …

Dietary Magnesium Replacement For Prevention Of Hypomagnesemia In Patients With Ovarian Cancer Receiving Carboplatin-Based Chemotherapy, Wenli Liu, Larissa Meyer, Meroë Morse, Yisheng Li, Juhee Song, Rosalinda Engle, Gabriel Lopez, Santhosshi Narayanan, Pamela T Soliman, Lois Ramondetta, Eduardo Bruera, Lorenzo Cohen

Faculty, Staff and Student Publications

Purpose: Hypomagnesemia is a common side effect of platinum-based chemotherapy and predicts poor overall survival in some cancers. Standard magnesium replacement strategies are often inadequate for maintaining magnesium levels. We hypothesized that a daily dietary magnesium replacement approach through magnesium-rich foods would help maintain adequate magnesium levels during platinum-based treatment.

Materials and methods: We conducted a prospective feasibility study of magnesium-rich diets in patients 18 years and older with previously untreated ovarian cancer scheduled to receive carboplatin-containing chemotherapy of at least six consecutive cycles. Education about magnesium-rich diets was provided at enrollment and then weekly during chemotherapy. Feasibility was defined …

A Randomized, Non-Comparative Phase 2 Study Of Neoadjuvant Immune-Checkpoint Blockade In Retroperitoneal Dedifferentiated Liposarcoma And Extremity/Truncal Undifferentiated Pleomorphic Sarcoma, Christina L Roland, Elise F Nassif Haddad, Emily Z Keung, Wei-Lien Wang, Alexander J Lazar, Heather Lin, Manoj Chelvanambi, Edwin R Parra, Khalida Wani, B Ashleigh Guadagnolo, Andrew J Bishop, Elizabeth M Burton, Kelly K Hunt, Keila E Torres, Barry W Feig, Christopher P Scally, Valerae O Lewis, Justin E Bird, Ravin Ratan, Dejka Araujo, M Alexandra Zarzour, Shreyaskumar Patel, Robert Benjamin, Anthony P Conley, J Andrew Livingston, Vinod Ravi, Hussein A Tawbi, Patrick P Lin, Bryan S Moon, Robert L Satcher, Bilal Mujtaba, Russell G Witt, Raymond S Traweek, Brandon Cope, Rossana Lazcano, Chia-Chin Wu, Xiao Zhou, Mohammad M Mohammad, Randy A Chu, Jianhua Zhang, Ashish Damania, Pranoti Sahasrabhojane, Taylor Tate, Kate Callahan, Sa Nguyen, Davis Ingram, Rohini Morey, Shadarra Crosby, Grace Mathew, Sheila Duncan, Cibelle F Lima, Jean-Yves Blay, Wolf Herman Fridman, Kenna Shaw, Ignacio Wistuba, Andrew Futreal, Nadim Ajami, Jennifer A Wargo, Neeta Somaiah

Faculty, Staff and Student Publications

Based on the demonstrated clinical activity of immune-checkpoint blockade (ICB) in advanced dedifferentiated liposarcoma (DDLPS) and undifferentiated pleomorphic sarcoma (UPS), we conducted a randomized, non-comparative phase 2 trial ( NCT03307616 ) of neoadjuvant nivolumab or nivolumab/ipilimumab in patients with resectable retroperitoneal DDLPS (n = 17) and extremity/truncal UPS (+ concurrent nivolumab/radiation therapy; n = 10). The primary end point of pathologic response (percent hyalinization) was a median of 8.8% in DDLPS and 89% in UPS. Secondary end points were the changes in immune infiltrate, radiographic response, 12- and 24-month relapse-free survival and overall survival. Lower densities of regulatory T cells …

Tp53 Mutation Is Frequent In Mantle Cell Lymphoma With Ezh2 Expression And Have Dismal Outcome When Both Are Present, Do Hwan Kim, Saima Siddiqui, Preetesh Jain, Michael Wang, Beenu Thakral, Shaoying Li, Roberto Miranda, Francisco Vega, L Jeffrey Medeiros, Chi Young Ok

Faculty, Staff and Student Publications

Enhancer of zeste homolog 2 (EZH2) expression is found in about 40% of mantle cell lymphoma (MCL) patients, which is associated with aggressive histology, high Ki-67 proliferation rate, p53 mutant pattern and inferior overall survival (OS). We conducted 11-gene (ATM, BIRC3, CCND1, KMT2C, KMT2D, NOTCH1, NOTCH2, RB1, TP53, TRAF2 and UBR5) next generation sequencing panel to shed more light on MCL with EZH2 expression (EZH2+ MCL). EZH2+ MCL more frequently harbor TP53 mutation compared to EZH2(-) MCL (41.2% vs. 19.1%, respectively, p = 0.045). TP53 mutation and EZH2 expression demonstrated overlapping features including aggressive histology, high Ki-67 proliferation rate and …

Tp53 Mutation Is Frequent In Mantle Cell Lymphoma With Ezh2 Expression And Have Dismal Outcome When Both Are Present, Do Hwan Kim, Saima Siddiqui, Preetesh Jain, Michael Wang, Beenu Thakral, Shaoying Li, Roberto Miranda, Francisco Vega, L Jeffrey Medeiros, Chi Young Ok

Faculty, Staff and Student Publications

Enhancer of zeste homolog 2 (EZH2) expression is found in about 40% of mantle cell lymphoma (MCL) patients, which is associated with aggressive histology, high Ki-67 proliferation rate, p53 mutant pattern and inferior overall survival (OS). We conducted 11-gene (ATM, BIRC3, CCND1, KMT2C, KMT2D, NOTCH1, NOTCH2, RB1, TP53, TRAF2 and UBR5) next generation sequencing panel to shed more light on MCL with EZH2 expression (EZH2+ MCL). EZH2+ MCL more frequently harbor TP53 mutation compared to EZH2(-) MCL (41.2% vs. 19.1%, respectively, p = 0.045). TP53 mutation and EZH2 expression demonstrated overlapping features including aggressive histology, high Ki-67 proliferation rate and …

Thematic Analysis Of Alzheimer's Medication Management Discussion In A Non-Moderated Online Forum, Jia Liu, Kylie Meyer, Ashlie Glassner, Mitzi Gonzales, Rebecca J Bartlett Ellis, Hyejin Park, Lixin Song, Neela Patel, Jing Wang

Faculty, Staff and Student Publications

Background: Managing medications for Alzheimer's disease and related dementias is challenging for caregivers. Information about caregivers' strategies to manage these challenges is needed to inform intervention development.

Objective: This study aimed to understand caregivers' medication management experiences by analyzing online community discussions.

Methods: Posts were extracted from the ALZConnected® Forum using keywords "medication" and "drug" via web scraping. The researchers applied thematic analysis.

Results: Four major themes emerged: (1) role transition of medication management responsibilities, (2) caregivers' uncertainty about medication purpose and values, (3) conflicts between the care recipients and caregivers, and (4) difficulty accessing and affording medications.

Conclusions: The …

The Value Of Global Collaborations, Chris Trauernicht, Laurence Court

Faculty, Staff and Student Publications

No abstract provided.